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In 2008 and 2015, respectively, Dr. Yeap underwent research attachment at the University of Oxford (UK) and Nippon Institute of Technology (Japan). Dr. Yeap is the external examiner and external course assessor of Wawasan Open University. He is also the Editor in Chief of the i-manager’s Journal on Digital Signal Processing. He has also been a guest editor for the Journal of Applied Environmental and Biological Sciences and Journal of Fundamental and Applied Sciences. Dr. Yeap has been given the university teaching excellence award, and 22 research grants. He has published more than 100 research articles (including refereed journal papers, conference proceedings, books, and book chapters). Prior to joining the academic industry, Dr. Yeap worked in Intel corporation in the pre-silicon validation group. He was awarded 4 Kudos awards by Intel for his contributions in the design and verification of the microchip’s design for testability (DFT) features.",institutionString:"Universiti Tunku Abdul Rahman",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:"Universiti Tunku Abdul Rahman",institutionURL:null,country:{name:"Malaysia"}}}],coeditorOne:{id:"454196",title:"Dr.",name:"Magdalene",middleName:null,surname:"Goh Wan Ching",slug:"magdalene-goh-wan-ching",fullName:"Magdalene Goh Wan Ching",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:"Dr Magdalene Goh Wan Ching\r\nDesignation: Senior lecturer\r\nQualifications: Diploma in Electrical & Electronics Engineering (Inti College), BEng in Electrical\r\nEngineering & Electronics (University of Liverpool, UK), PhD in Solid State\r\nDevice Physics & RF Transistors Design (University of Liverpool, UK)\r\n\r\nProfessional Body\r\nMemberships:\r\n\r\nInaugural Senior Member, International Engineering & Technology Institute\r\n(IETI), Hong Kong\r\n\r\nBiodata: Dr. Magdalene Goh obtained her Diploma in Electrical & Electronics Engineering\r\nfrom Inti College before leaving for the UK to pursue her BEng in Electrical\r\nEngineering & Electronics and later on, her PhD. Prior to joining the academia,\r\nshe has worked for a few years in the industry in the areas of semiconductor\r\nprocess technology, silicon wafer characterizations, mask layout design,\r\nanalogue circuits design and design for testability (DFT). While in the academic,\r\nshe had served as a judge for Innovate Malaysia undergraduate final year\r\nprojects competition from 2012 - 2015. She had served as an external examiner\r\nfor a PhD candidate from VIT University, India in 2013, and an external examiner\r\nfor SEGi College Penang from 2014 – 2018. She has been actively involved with\r\nthe Penang Science Cluster in their radio telescope team since 2014, where she\r\nworks with a team of volunteers (from both academia and the industry in\r\nPenang) to create curricula in radio astronomy, for the purpose of introducing the\r\nconcepts of radio astronomy and radio telescopes to both school pupils and\r\ncollege students. She has been a member of the Astronomical Society of\r\nPenang since 2016.\r\n\r\nCourse Development\r\nExperience:\r\n\r\nSince joining WOU, Dr. Goh has developed eight courses, namely Control\r\nSystems, Microprocessors, Digital Communications, Microelectronics, VLSI\r\nDesign, Process Control & Instrumentation, Power Electronics & Drives and\r\nElectrical Power & Drives.\r\n\r\nResearch Interest: Dr. Goh’s research interests are in the areas of semiconductor physics and\r\nelectromagnetics. She also has strong interest in the field of astronomy and is\r\nworking with a group of volunteers to promote astronomy education in the\r\nsecondary schools in Penang. She had also worked with some interns on the\r\nradio telescope project at the Penang Science Cluster.\r\n\r\nResearch Projects and\r\nConsultancy Work:\r\nSelected Publications: Design of Radio Frequency Metal-Insulator-Metal (MIM) Capacitors. \r\n\r\nExperimental Investigation on Thermoelectric Generator for Battery - Charger\r\nBased Oven.\r\nAnalyzing the Physics of Radio Telescopes and Radio Astronomy (book\r\nchapters).\r\n\r\nConferences,\r\nSeminars and\r\nWorkshops:\r\n\r\nDr. Goh was appointed as one of the Technical Committee Member for the\r\nVirtual Conference on Electronics and Communication: Loading Intelligence on\r\nFuture Electronics (October 2020).\r\n\r\nHonorary\r\nAppointments and\r\nAwards:\r\n\r\nDr. Goh is a reviewer of the following journals:-\r\n1. Microwave and Optical Technology Letters.\r\n2. Journal of Electrical Engineering.\r\n3. 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Pavel",slug:"marilena-d.-pavel"}]},{id:"19532",title:"Concurrent Subspace Optimization for Aircraft System Design",slug:"concurrent-subspace-optimization-for-aircraft-system-design",signatures:"Ke-shi Zhang",authors:[{id:"33820",title:"Dr.",name:"Ke-Shi",middleName:null,surname:"Zhang",fullName:"Ke-Shi Zhang",slug:"ke-shi-zhang"}]},{id:"19533",title:"The Assessment Method for Multi-Azimuth and Multi-Frequency Dynamic Integrated Stealth Performance of Aircraft",slug:"the-assessment-method-for-multi-azimuth-and-multi-frequency-dynamic-integrated-stealth-performance-o",signatures:"Ying Li, Jun Huang, Nanyu Chen and Yang Zhang",authors:[{id:"29830",title:"Dr.",name:"Ying",middleName:null,surname:"Li",fullName:"Ying Li",slug:"ying-li"},{id:"35587",title:"Prof.",name:"Jun",middleName:null,surname:"Huang",fullName:"Jun Huang",slug:"jun-huang"},{id:"92596",title:"Dr.",name:"Chen",middleName:null,surname:"Nanyu",fullName:"Chen Nanyu",slug:"chen-nanyu"},{id:"92597",title:"MSc.",name:"Yang",middleName:null,surname:"Zhang",fullName:"Yang Zhang",slug:"yang-zhang"}]},{id:"19534",title:"Aircraft Gas-Turbine Engine’s Control Based on the Fuel Injection Control",slug:"aircraft-gas-turbine-engine-s-control-based-on-the-fuel-injection-control",signatures:"Alexandru-Nicolae Tudosie",authors:[{id:"30042",title:"Dr.",name:"Alexandru Nicolae",middleName:"Nicolae",surname:"Tudosie",fullName:"Alexandru Nicolae Tudosie",slug:"alexandru-nicolae-tudosie"}]},{id:"19535",title:"Plasma-Assisted Ignition and Combustion",slug:"plasma-assisted-ignition-and-combustion",signatures:"Andrey Starikovskiy and Nickolay Aleksandrov",authors:[{id:"29275",title:"Dr.",name:"Andrey",middleName:null,surname:"Starikovskiy",fullName:"Andrey Starikovskiy",slug:"andrey-starikovskiy"},{id:"47602",title:"Prof.",name:"Nikolay",middleName:null,surname:"Aleksandrov",fullName:"Nikolay Aleksandrov",slug:"nikolay-aleksandrov"}]},{id:"19536",title:"O2/CH4 Kinetic Mechanisms for Aerospace Applications at Low Pressure and Temperature, Validity Ranges and Comparison",slug:"o2-ch4-kinetic-mechanisms-for-aerospace-applications-at-low-pressure-and-temperature-validity-ranges",signatures:"Angelo Minotti",authors:[{id:"42740",title:"Dr.",name:"Angelo",middleName:null,surname:"Minotti",fullName:"Angelo Minotti",slug:"angelo-minotti"}]},{id:"19537",title:"Creep Behaviors and Influence Factors of FGH95 Nickel-Base Superalloy",slug:"creep-behaviors-and-influence-factors-of-fgh95-nickel-base-superalloy",signatures:"Tian Sugui and Xie Jun",authors:[{id:"45197",title:"Dr.",name:"Tian",middleName:null,surname:"Sugui",fullName:"Tian Sugui",slug:"tian-sugui"}]},{id:"19538",title:"Multi-Dimensional Calibration of Impact Models",slug:"multi-dimensional-calibration-of-impact-models",signatures:"Lucas G. Horta, Mercedes C. Reaves, Martin S. Annett and Karen E. Jackson",authors:[{id:"44055",title:"Dr.",name:"Lucas",middleName:null,surname:"Horta",fullName:"Lucas Horta",slug:"lucas-horta"}]},{id:"19539",title:"An Agile Cost Estimating Methodology for Aerospace Procurement Operations: Genetic Causal Cost CENTRE-ing",slug:"an-agile-cost-estimating-methodology-for-aerospace-procurement-operations-genetic-causal-cost-centre",signatures:"R. Curran, P. Watson and S. Cowan",authors:[{id:"64523",title:"Prof.",name:"Ricky",middleName:null,surname:"Curran",fullName:"Ricky Curran",slug:"ricky-curran"}]},{id:"19540",title:"Developing Risk Models for Aviation Inspection and Maintenance Tasks",slug:"developing-risk-models-for-aviation-inspection-and-maintenance-tasks",signatures:"Lee T. Ostrom and Cheryl A. Wilhelmsen",authors:[{id:"42015",title:"Dr.",name:"Lee",middleName:null,surname:"Ostrom",fullName:"Lee Ostrom",slug:"lee-ostrom"},{id:"85274",title:"Prof.",name:"Cheryl",middleName:null,surname:"Wilhelmsen",fullName:"Cheryl Wilhelmsen",slug:"cheryl-wilhelmsen"}]},{id:"19541",title:"Novel Digital Magnetometer for Atmospheric and Space Studies (DIMAGORAS)",slug:"novel-digital-magnetometer-for-atmospheric-and-space-studies-dimagoras-",signatures:"George Dekoulis",authors:[{id:"9833",title:"Prof.",name:"George",middleName:null,surname:"Dekoulis",fullName:"George Dekoulis",slug:"george-dekoulis"}]},{id:"19542",title:"Aeronautical Data Networks",slug:"aeronautical-data-networks",signatures:"Mustafa Cenk Erturk, Wilfrido Moreno, Jamal Haque and Huseyin Arslan",authors:[{id:"33703",title:"MSc",name:"Mustafa Cenk",middleName:null,surname:"Erturk",fullName:"Mustafa Cenk Erturk",slug:"mustafa-cenk-erturk"},{id:"45737",title:"MSc.",name:"Jamal",middleName:null,surname:"Haque",fullName:"Jamal Haque",slug:"jamal-haque"},{id:"83108",title:"Prof.",name:"Huseyin",middleName:null,surname:"Arslan",fullName:"Huseyin Arslan",slug:"huseyin-arslan"}]},{id:"19543",title:"Air Traffic Control Decision Support for Integrated Community Noise Management",slug:"air-traffic-control-decision-support-for-integrated-community-noise-management",signatures:"Sander J. Hebly and Hendrikus G. Visser",authors:[{id:"62534",title:"Dr.",name:"Hendrikus",middleName:null,surname:"Visser",fullName:"Hendrikus Visser",slug:"hendrikus-visser"}]},{id:"19544",title:"A Conceptual Framework and a Review of Conflict Sensing, Detection, Awareness and Escape Maneuvering Methods for UAVs",slug:"a-conceptual-framework-and-a-review-of-conflict-sensing-detection-awareness-and-escape-maneuvering-m",signatures:"B. M. Albaker and N. A. Rahim",authors:[{id:"28485",title:"Prof.",name:"Nasrudin",middleName:null,surname:"Abd. Rahim",fullName:"Nasrudin Abd. 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Ghijs",authors:[{id:"64523",title:"Prof.",name:"Ricky",middleName:null,surname:"Curran",fullName:"Ricky Curran",slug:"ricky-curran"},{id:"64035",title:"Dr.",name:"Frank",middleName:null,surname:"Van Der Zwan",fullName:"Frank Van Der Zwan",slug:"frank-van-der-zwan"}]}]}],publishedBooks:[{type:"book",id:"5136",title:"Recent Progress in Some Aircraft Technologies",subtitle:null,isOpenForSubmission:!1,hash:"6855bfb94011b56313a07020fa05ead6",slug:"recent-progress-in-some-aircraft-technologies",bookSignature:"Ramesh K. Agarwal",coverURL:"https://cdn.intechopen.com/books/images_new/5136.jpg",editedByType:"Edited by",editors:[{id:"38519",title:"Prof.",name:"Ramesh K.",surname:"Agarwal",slug:"ramesh-k.-agarwal",fullName:"Ramesh K. 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When metabolized into the active hormone calcitriol, it can bind to vitamin D receptors (VDRs). These VDRs are expressed by most cells in the human body, allowing vitamin D to have a broad range of functions. Upon binding of vitamin D to a VDR, gene transcription is altered. All types of immune cells in the human body express the vitamin D receptor, enabling vitamin D to alter immune responses [1]. In general, vitamin D has immunosuppressive properties and can therefore be beneficial in diseases characterized by inflammation and autoimmunity such as multiple sclerosis and inflammatory bowel disease [2]. Vitamin D deficiency is an increasing global problem with an estimated 30% of the population suffering from vitamin D deficiency and 60% being vitamin D insufficient [3]. Inadequate levels of vitamin D can have many adverse effects throughout the body due to the abundant expression of VDRs. Furthermore, maternal vitamin D deficiency has been suggested to affect development of the offspring. To date, the World Health Organization does not recommend vitamin D supplementation to pregnant women. This illustrates the lack of awareness on the importance of vitamin D in health.
A disorder that recently received increased attention is autism spectrum disorder (ASD). ASD is a heterogeneous neurodevelopmental disorder, collectively describing autistic disorder, Asperger’s syndrome and Pervasive Developmental Disorders Not Otherwise Specified (PDD-NOS). It is characterized by behavioral deficits, impaired communicative functioning and restricted and repetitive patterns of behavior [4]. ASD onset usually occurs in the first few years of life and proceeds into childhood and adulthood [5]. Genetics are of importance in the disorder – several studies show monozygotic twins share 60–90% of ASD symptoms [5, 6]. Additionally, ASD is four times more prevalent in boys, which is suggested to be due to the protective effects of estrogens in women [5, 7].
Despite the role of genetics, the prevalence of ASD has increased tremendously over the past few decades [8]. In the Netherlands, the prevalence of ASD increased from 90.000 to 190.000 cases between 2001 and 2009 [9]. More recently, the prevalence of ASD in the US was estimated at one in every 59 children aged eight years in 2014, which increased to one in every 54 children in 2016 [10]. Across all ages, the prevalence of ASD is estimated to be 1% of the worldwide population [11, 12]. Partially, this increase can be explained by improved diagnostics and increased awareness. However, the sudden and rapid increase also suggests the role of environmental factors in ASD onset. Research indicates that genetic predisposition predominates, requiring additional environmental triggers to develop ASD. Multiple environmental factors have been suggested, including antibiotic use, maternal infections during pregnancy and sun exposure. The strong increase in prevalence highlights the importance of understanding the role of environmental factors in the etiology of ASD [6].
The association between vitamin D and ASD was suggested in 2008 when it was observed that the increase in ASD prevalence coincides with the medical advice to avoid sun exposure [7]. Since then, clinical trials have been performed, trying to prove the association between vitamin D and ASD. UV-B is the most important source of vitamin D in humans, illustrating the requirement for sunlight. Research shows ASD prevalence is higher in countries at higher latitudes, coinciding with reduced UV-B intensity. Moreover, ASD patients consistently exhibit lower vitamin D levels than healthy individuals and studies have shown maternal vitamin D deficiency increases the risk of ASD. These findings encouraged scientists to study the effect of vitamin D supplementation on improving ASD symptoms, and thus far promising results have been found [7, 13]. Yet, the mechanisms behind the possible association between vitamin D and ASD remain unknown. Neuroinflammation, oxidative stress, autoimmunity and immune dysregulation are all observed in individuals with ASD [14]. Of these phenomena, immune dysregulation is the least well-described in literature. ASD patients suffer from chronic systemic inflammation, which is illustrated by a disbalance in cytokine expression and the presence of comorbidities such as gastrointestinal problems in a large fraction of ASD patients [15]. Increased immune activation is observed in ASD patients and is associated with more severe symptoms [16]. Taking into consideration the immunosuppressive properties of vitamin D, this suggests that perhaps vitamin D could play a role in rebalancing the dysregulated immune system in ASD patients and thereby reduce systemic inflammation. However, to date there is no recommendation for vitamin D supplementation in ASD patients.
Therefore, in this review the role of vitamin D in immune dysregulation in ASD patients is examined. First, immunomodulatory properties of vitamin D in general and peripheral immune dysregulation in ASD are described, with a focus on CD4+ T cell activity. Next, possible mechanisms behind this effect of vitamin D on immune dysregulation in ASD are discussed. This review is summarizing current knowledge on vitamin D and ASD and to examine possible mechanisms via which vitamin D might slow ASD development.
Vitamin D is a steroid hormone with varying functions in the human body. Vitamin D precursors are extracted both from food and through the exposure to sunlight. Around 10% of the total amount of vitamin D in the body is provided by dietary sources and supplements [17]. There are two forms of vitamin D precursors: D2 (ergocalciferol) and D3 (cholecalciferol). Some plant products are rich in vitamin D2, whereas vitamin D3 is present in animal products, including fish and egg yolk [18]. Sunlight exposure accounts for about 90% of vitamin D and is thus the most important source of this vitamin [17]. When the human skin is exposed to UV-B, 7-dehydrocholesterol is converted into pre-vitamin D [19]. This process depends on factors such as UV-B intensity, skin color and coverage of the skin.
After the production of vitamin D3 in the body, it is first metabolized into the precursor 25-hydroxyvitamin D (25(OH)D). This reaction is performed in the liver by hydroxylases, of which CYP2R1 has the highest affinity for pre-vitamin D [20]. Vitamin D binding protein functions as a transporter of 25(OH)D to the kidney. Consequently, 1,25-dihydroxyvitamin D (1,25(OH)2D) is formed in the kidney by the enzyme CYP27B1. The activity of this enzyme is essential to produce bioactive vitamin D. 1,25(OH)2D is the hormonally active form of vitamin D [21]. In this review 1,25 (OH)2D reflects bioactive vitamin D. Besides renal CYP27B1, other cells in the human body can also express this enzyme. In this way, vitamin D can be directly synthesized not solely in the kidney but also in other tissues [20]. 1,25(OH)2D can be absorbed and then bind to the intracellular vitamin D receptor (VDR). Due to the lack of 1,25(OH)2D in its free form in the blood, vitamin D levels are based on 25(OH)D. This precursor is bound to vitamin D binding protein (DBP) in the circulation, allowing measurements to determine vitamin D levels [22, 23].
1,25(OH)2D can influence its own serum levels and binding to VDR. When serum 1,25(OH)2D levels are high, this enhances VDR expression. Moreover, 1,25(OH)2D has a negative feedback on CYP27B1, the enzyme involved in 1,25(OH)2D synthesis. Besides self-regulation, parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) are important regulators of vitamin D metabolism. To sustain normal systemic vitamin D levels, CYP24A1 is stimulated by 1,25(OH)2D and degrades vitamin D. The CYP24A1 enzyme is present in all vitamin D target cells, resulting in the ability to regulate intracellular vitamin D levels [20].
By binding to VDR, which has a DNA-binding domain, 1,25(OH)2D can exert effects on the body through gene transcription. VDRs are located intracellularly in a wide range of cells. Due to this, vitamin D can exert effects on many different biological processes in the body [21, 24]. The regulation of genes by VDR is cell specific. After the binding of vitamin D to VDR, VDR interacts with the retinoic X receptor (RXR). The VDR/RXR heterodimer binds to vitamin D responsive elements (VDRE) in the promoter region of vitamin D responsive genes, influencing gene transcription [21, 25]. These VDREs are upstream of many genes and thereby exert an effect on different functions of the body. The most well-known activity of vitamin D in the body is its role in calcium homeostasis. By stimulating calcium absorption, vitamin D enhances bone density. However, vitamin D also plays a role in many other biological processes, including the control of cancer cell proliferation, skin function, cardiovascular disease and regulation of the immune system [20]. It has vasculo-protective roles, especially in blood vessels that are sensitive to inflammation [26]. Moreover, vitamin D is important in neurocognitive development through its stimulation of nerve growth factor production [27].
Vitamin D has also been described to affect both innate and adaptive immunity and is therefore considered to be immunomodulatory, including control of effector functions, increasing barrier function and stimulating regulatory T cells [28]. 1,25(OH)2D binds to a VDR which is located intracellularly. Consequently, the VDR/RXR complex translocates to the nucleus and binds to a VDRE, thereby altering gene transcription [29]. Studies show that the required 1,25(OH)2D levels are likely to be higher than the average serum vitamin D levels to facilitate immunomodulation. To maintain bone health, 1,25(OH)2D serum levels should be around 20 ng/mL or higher [30]. In contrast, 1,25(OH)2D levels should approximately be 40–80 ng/mL to reach sufficient amounts necessary for immunomodulation. These high 1,25(OH)2D levels can be achieved by the autocrine and paracrine functions of immune cells regarding vitamin D [31]. As stated before, vitamin D exerts its effects through VDRs. These receptors are expressed in all immune cells, although in ranging amounts [31]. By binding of 1,25(OH)2D to VDRs, vitamin D can activate or suppress gene transcription. Additionally, 1,25(OH)2D can exert rapid non-genomic responses. In contrast to genomic responses which require hours to days to become apparent, these rapid responses take 1 to 45 minutes [32]. Unfortunately, the exact mechanism of how this works has yet to be discovered.
Interestingly, immune cells can also affect 1,25(OH)2D levels. Most immune cells, including macrophages and dendritic cells, express CYP27B1 and CYP24A1, the enzymes needed for active vitamin D synthesis and degradation respectively. This allows immune cells to directly control 1,25(OH)2D levels in their direct local microenvironment, exerting autocrine and paracrine effects [33, 34]. This contrasts with systemic 1,25(OH)2D levels, which are regulated by CYP27B1, PTH and FGF23. Previous studies show that the negative feedback loop present in renal CYP24A1 and 1,25(OH)2D does not apply to immune cell hydroxylases. Due to this, CYP24A1 is not activated by high levels of 1,25(OH)2D, resulting in increased vitamin D levels [35].
ASD is characterized not only by behavioral deficits, but also by comorbidities, including gastrointestinal problems. In addition, there is an involvement of the immune system based on the increased inflammation, autoimmunity and oxidative stress in ASD patients compared to healthy individuals [36]. Additionally, the prevalence of allergies and infections among ASD patients is higher compared to healthy individuals [37, 38]. A recent study states that approximately 60% of all ASD patients suffers from immune dysregulation [39, 40].
Studies indicate that innate immune activation with activated antigen presenting cells and associated cytokine production is observed in ASD patients [41]. Increased numbers of monocytes with increased amounts of cytokines, with a shift towards pro-inflammatory cytokines are found in ASD patients compared to healthy individuals. IL-1β is one of these cytokines and is associated with more severe ASD symptoms. Upon TLR signaling, monocytes in ASD patients show increased activation and pro-inflammatory cytokine production [42, 43]. Macrophage or microglial activity associated with increased production of macrophage migration inhibitory factor (MIF) neuroinflammation in the brain is also altered in ASD patients [44]. MIF is a mediator of innate immunity by enhancing pro-inflammatory cytokine release and higher MIF levels result in less suppression of macrophage activity. Moreover, MIF levels are positively correlated with increased macrophage activity and thus ASD severity [45, 46]. Individuals with ASD show an increased number of dendritic cells, which is associated with more severe ASD symptoms [47]. These different findings thus illustrate increased innate immune activation in ASD patients.
Monocyte and macrophage activity are increased in ASD patients, both due to increased cell numbers and increased pro-inflammatory cytokine production. Contradictory, vitamin D suppresses pro-inflammatory cytokine release by M1 macrophages, while antimicrobial activities and differentiation into M2 macrophages are stimulated. Like a balance between Th1 and Th2 cells, a balance between M1 and M2 macrophages is required for immune homeostasis. An increase in both types of macrophages could thus be beneficial, if a balance is maintained [48, 49]. Altogether, vitamin D balances macrophage function and is thereby likely to positively affect macrophage function in ASD patients. The number of dendritic cells is also increased in individuals with ASD, resulting in increased T cell activation and, indirectly, development of more severe symptoms [47]. In contrast, vitamin D can induce a tolerogenic state in dendritic cells. The expression of surface molecules required for antigen presentation and T cell activation is inhibited and a shift from pro-inflammatory to anti-inflammatory cytokine secretion arises. Via these pathways, vitamin D could affect dendritic cells in ASD patients in such a way that it facilitates immunosuppression. Besides altered cytokine profiles that illustrate changes in CD4+ T cell differentiation, this shift in subsets is also shown by absolute cell numbers. Increased Th1 and Th17 populations are observed in ASD patients, combined with a decreased Treg population. Moreover, Tregs exhibit a reduced expression of Foxp3, CD25 and CTLA-4, which are all required for regulation of immune responses. Opposingly, vitamin D positively influences Th2 and Treg populations and hereby shifts immune responses to a more anti-inflammatory state [50, 51].
Altered cytokine expression has been observed in ASD patients with increased levels of pro-inflammatory cytokines IFN-y, IL-6, TNF-alpha, IL-8, IL-12, IL-17, IL-1ß, GM-CSF and MCP-1. IL-2 and IL-23. A meta-analysis described the strongest elevations were seen for IFN-y and thus Th1 cells stimulating inflammation and inhibiting Th2 proliferation in ASD patients compared to healthy individuals [52]. Besides, IL-6 is increased which as an important B cell activator enhances antibody production. In addition, IL-6 induces innate immune responses via the production of acute phase proteins [53]. Besides, IL-6 is important in signaling pathways in the central nervous system (CNS) by impairing synaptic plasticity and mediating behavioral deficits seen in ASD patients [54, 55]. IL-1ß has been shown to play a role in depression and anxiety through the hypothalamus-pituitary–adrenal (HPA) axis. Moreover, the role of IL-1ß has been suggested in training of the immune system. Upon excessive IL-1ß production, the immune system is characterized by less tolerance induction and increased prevalence of chronic inflammation [56]. However, a study reported no change in IL-1ß levels in ASD patients [57].
A study described significantly increased TNF-alpha, IL-6 and IL-17 levels and a decrease in IL-2 by peripheral blood samples of thirty ASD individuals compared to healthy controls [58]. Another study did not find significant alterations in IL-2 levels of ASD patients compared to healthy individuals [59]. TNF-alpha and IL-12 expression are consistently proven to be elevated in ASD patients [57, 60]. IL-17 expression is shown either to be increased [61, 62, 63] or similar in ASD patients compared to healthy individuals [64, 65]. Besides IL-17, IL-21 and IL-22 are two other important Th17 cytokines. These are both shown to be increasingly expressed in ASD patients [66]. Contradicting findings exist on the expression of IL-23, a cytokine important in Th17 differentiation [64, 65, 67]. GM-CSF is shown to be elevated in ASD patients. This cytokine is important in the activation of Th17 cells and hereby plays a role in autoimmunity [68]. Contradictory, GM-CSF is also suggested to have beneficial effects on ASD symptoms. For example, GM-CSF can cross the blood brain barrier and can act as neuronal growth factor [68]. GM-CSF was associated with improved development and behavior in ASD patients. Several chemokines, including IL-8 and MCP-1, are also elevated in ASD patients. These chemokines have the capacity to attract T cells to tissue inflammation sites [69].
Several studies observe alterations in anti-inflammatory cytokines in ASD patients, like reductions in TGF-ß expression [70, 71]. TGF-ß being involved in immune regulation and is associated with severity of ASD symptoms; the lower the TGF-ß status, the more severe ASD symptoms are [72]. The levels of IL-10 in ASD patients remain debatable. Some studies observed increased IL-10 levels [69], while others found similar IL-10 levels [73] or even lower IL-10 levels [71, 74] in ASD patients compared to healthy individuals. IL-10 modulates inflammatory response and thus the observed increased inflammation in ASD patients could be expected to be increased. Lack of this compensatory activity of IL-10 suggests immune dysregulation. Lastly, IL-35 is also connected to regulatory T cells and was found to be reduced in ASD patients [75]. Meta-analysis findings suggest that the changes in IL-4, IL-5 and IL-13 levels in ASD patients are insignificant [70]. On the other hand, multiple studies observe increased concentrations of IL-4, IL-5 and IL-13 in ASD patients [76]. In general, a decreased level of anti-inflammatory cytokines is found in ASD patients. This can result in chronic inflammation in ASD patients [6].
In summary, pro-inflammatory cytokines and chemokines are all increasingly expressed in ASD patients while anti-inflammatory cytokines are downregulated. Nevertheless, other studies showed an increased expression of anti-inflammatory cytokines combined with a decreased expression of pro-inflammatory cytokines upon vitamin D treatment. Upon exposure to vitamin D, immune cells secrete increased amounts of the anti-inflammatory cytokines IL-10 and TGF-ß. At the same time vitamin D suppresses the production of pro-inflammatory cytokines and chemokines. This cytokine expression profile indicates that vitamin D might have protective effects against ASD development.
In general, an increase in inflammatory Th1 and Th17 cells can be observed in individuals with ASD and were directly correlated with severity of symptoms [71, 77]. In contrast, increased Th2 responses are associated with improved behavior in children with ASD [72]. This suggests also beneficial effects of a Th2-skewed immune system in ASD patients. While mostly an increased Th1/Th2 ratio is observed in ASD patients compared to healthy individuals [78], others describe increased Th2 relative to Th1 [72]. This contrast illustrates immune dysregulation in ASD patients [70]. In addition, a decreased Foxp3 expression positive Treg population is observed [] as well as decreased CTLA-4 expression [72]. Also, CD25 expression in activated CD4+ and CD8+ T cells is decreased [66, 71], while others showed a decreased ratio [79].
The observed dysregulation of the immune system in individuals with ASD is important not only for developing symptoms, but also affects the severity of the symptoms. In general, it can be concluded that ASD patients have increased Th1- and Th17-mediated immune responses and decreased Th2 and Tregs cytokines. Due to the increased immune activation, chronic inflammation can occur and worsen ASD symptoms. Children with genetic heritability have a higher chance of developing ASD, and the role of a disbalanced immune system in ASD development should be acknowledged.
In addition to peripheral immune dysregulation in ASD, other immunological dysfunctions in ASD are also of importance. The role of neuroinflammation, autoimmunity and oxidative stress have been investigated more widely in ASD patients and the importance of these processes should be noted. The difference between systemic inflammation and neuroinflammation is reflected by the fact that some cytokines are differentially expressed in the brain versus systemically. Increased TGF-ß levels are measured in the cerebellum of ASD patients, in contrast to decreased levels in the cerebrospinal fluid or the periphery [80]. Upon cell death, cells often secrete TGF-ß to reduce local inflammation. Neurons that showed degeneration were high in TGF-ß, suggesting the increased TGF-ß levels found in the brain of ASD patients are targeted at controlling neuroinflammation. Increased microglial activation, combined with increased pro-inflammatory cytokines and i-NOS activation results in neuroinflammation [41]. This is observed in a large fraction of all ASD cases and could lead to impaired connectivity in the CNS, resulting in the pathophysiology observed in ASD patients. Moreover, oxidative stress is increased in ASD patients, which is among others shown by increased i-NOS activation and the presence of reactive oxygen species. Oxidative stress can affect both immune cells and neurons, thereby causing neuroinflammation and neuron degeneration [36]. Vitamin D has been shown to increase glutamine, an antioxidant capable of counteracting the negative activities of free oxygen radicals, and to decrease nitric oxide. Via these ways, vitamin D could reduce oxidative stress in ASD patients [13].
Lastly, improving ASD symptoms is touched upon most in this review by discussing immune dysregulation in ASD, prevention of ASD is another topic that requires attention. While vitamin D is presumed to play a role in immune dysregulation, and thereby systemic inflammation in ASD patients, this is thought to be limited to the progression of ASD symptoms. ASD is a neurodevelopmental disorder, indicating the importance of the CNS in the etiology and pathophysiology of ASD. Considering the onset of ASD, neuroinflammation, rather than systemic inflammation, should be focused on. Vitamin D is proven to play an important role in neuronal development, which is also illustrated by the abundance of VDRs in the CNS [81]. Maternal vitamin D deficiency and risk of ASD have been commonly shown to be associated. When maternal vitamin D deficiency occurs, insufficient vitamin D impairs neurodevelopment in the infant [82] This illustrates the importance of adequate vitamin D levels during gestation. A recent study tested the efficacy of vitamin D supplementation in pregnant mothers of children with autism on reducing the risk of autism in the newborn sibling [83]. After maternal vitamin D supplementation and supplementation during the first three years of the newborn’s lives, the risk of autism was shown to be reduced from 20% to 5%. This illustrates the importance of adequate maternal vitamin D status and the influence on ASD risk. Vitamin D supplementation is likely to be effective at reducing inflammation in ASD patients and improve symptoms of ASD. However, to prevent ASD it is more relevant to look at maternal vitamin D supplementation and the role of vitamin D in neurodevelopment. Therefore, further research should be performed to examine the possible mechanisms of vitamin D during gestation and the association with ASD development in the infant.
The possibility of an association between vitamin D and ASD was found when studies concluded that ASD prevalence is increased in high-latitude countries and with more cloud coverage, resulting in reduced UV-B intensity. Many studies observe the connection between low sun exposure and risk of ASD [84]. UV-B exposure is required for the conversion of 7-dehydrocholesterol into previtamin D underscoring the link between UV exposure, vitamin D generation and ASD development [85]. However, it was shown that vitamin D insufficiency in ASD patients is independent of sun exposure, ruling out the environmental factor causing vitamin D deficiency later in life. Moreover, ASD prevalence is suggested to be higher in dark skin-colored people compared to light skin-colored people [86]. It is suggested that increased skin pigmentation lowers the production of previtamin D, due to UV-B radiation that is absorbed by melanin and thereby less available for vitamin D synthesis [11]. For example, a study showed only 4.1% of the dark skin-colored pregnant women had sufficient vitamin D levels, compared to 37.3% in light skin-colored pregnant women [87]. However, other studies state skin pigmentation does not influence vitamin D synthesis and that a different lifestyle, i.e. less exposure to sunlight, could explain lower vitamin D levels in dark skin-colored people [88, 89]. Thus, common vitamin D deficiency in dark skin-colored people might explain the higher ASD prevalence among this group, however results are contradictory regarding the cause of lower vitamin D status.
ASD prevalence is increased in children of whom the mother was vitamin D deficient during gestation [87] and thus it is suggested that maternal vitamin D deficiency increases the risk of ASD in the infant [84, 90].
The possible role of maternal vitamin D deficiency is also illustrated by the influence of season of birth on ASD risk. Maternal vitamin D levels are often lowest in winter and spring months [91], which could be explained by differences in sun exposure and UV-B intensity [85, 91]. However, studies observe conflicting results regarding seasons most positively associated with ASD risk, questioning whether birth season is indeed a cofactor influencing the risk of ASD. Multiple studies observe highest ASD prevalence in children born in March [92]. These children have a higher risk of maternal vitamin D deficiency in the second half of gestation, since maternal 25(OH)D levels are lowest in winter and spring months. On the other hand, studies observing highest ASD prevalence among children born in May, July or August also exist [93, 94, 95]. Autumn months coincided with highest ASD prevalence, while birth in spring months reduced the risk of ASD [96]. Studies show that the first six months of gestation are most important for neurocognitive development in the infant, a process which is influenced by vitamin D [97, 98]. Therefore, it is suggested that maternal vitamin D deficiency increases the risk of ASD most when occurring in the first six months of gestation. As vitamin D levels are lowest in winter and spring, this would result in highest ASD prevalence among children who are born in summer. However, contradicting results on the association between birth season and ASD risk hinder a definite conclusion.
Studies show that children with ASD have lower vitamin D levels than healthy children. Since 2011, vitamin D insufficiency is classified as a 25(OH)D level between 20–30 ng/mL, whereas levels below 20 ng/mL are considered vitamin D deficient [3]. Individuals with ASD on average show 25(OH)D levels below 30 ng/mL [99, 100, 101]. In a recent study, 48% of the ASD cases was vitamin D insufficient and 40% vitamin D deficient, whereas none of the healthy children were deficient and only 20% was insufficient [101]. This study used different cut-off values, resulting in the fact that when using the standard cut-off of 20 ng/mL for vitamin D deficiency, the percentage of deficient children would even be higher than 40%. An average vitamin D level of 28.5 ng/mL was measured in ASD children, compared to 40.1 ng/mL in healthy children [102]. A significant negative correlation between vitamin D levels and severity of ASD symptoms was found, indicating low vitamin D levels can increase the severity of ASD [100]. When combining this finding with the previously mentioned association between season and vitamin D levels, this suggests the effect of season on ASD symptoms. Several case studies indeed observe that children with ASD experience less symptoms during summer compared to other seasons, which supports the plausible association between vitamin D and ASD [103].
In addition to the above-mentioned environmental factors that could cause vitamin D deficiency in ASD patients and are associated with progression of the disorder, genetics also play a role. In a study that compared vitamin D levels in ASD children and their healthy siblings, lower 25(OH)D levels were found in ASD children, suggesting genetics are upstream of vitamin D deficiency in ASD patients, rather than environmental factors [104]. Moreover, most studies on neonatal vitamin D levels and the association with ASD risk have found a negative correlation, illustrating that vitamin D deficiency presumably develops during gestation and is dependent on either or both genetics and maternal environmental factors [105, 106].
Furthermore, genetic polymorphisms are shown to be associated with impaired vitamin D metabolism and binding to VDR and can therefore predispose ASD. VDR gene polymorphisms were studied of which two were significantly associated with ASD [86]. Measured 25(OH)D serum levels did not significantly correlate with gene polymorphisms, suggesting vitamin D deficiency itself is not the cause of increased ASD risk, but rather genetic mutations. However, not all ASD patients suffer from these gene mutations and thus gene polymorphisms cannot explain all ASD cases [107]. To conclude, it is uncertain whether genetic or environmental factors alone predispose vitamin D deficiency in ASD patients. Nonetheless, clinical trials agree that reduced vitamin D levels are observed in ASD patients.
Due to the suggested association between vitamin D levels and ASD symptom severity, it is being investigated whether vitamin D supplementation could work as treatment to reduce ASD symptoms. The effect of vitamin D, n-3 fatty acids and the combination of the two were tested on ASD symptoms [108]. In the study, children with ASD received a daily dose of 2000 IU vitamin D3 for twelve months. This study did not find a positive effect of only vitamin D supplementation on reducing ASD symptoms. However, treatment with n-3 fatty acids only or the combined treatment with vitamin D and n-3 fatty acids did improve social awareness scores in children with ASD. In contrast, a positive effect of vitamin D treatment was observed on ASD symptoms [109]. Autism Behavior Checklist (ABC) and Childhood Autism Rating Scale (CARS) scores were used, two methods commonly used for scoring ASD symptoms. Children with ASD received one monthly dose of 150,000 IU vitamin D intramuscularly and daily doses of 400 IU vitamin D orally. After three months, both total ABC and total CARS scored were decreased significantly. These reductions were prominent in ASD children under the age of three compared to ASD children above the age of three, suggesting vitamin D treatment possibly is more effective at a younger age. Similarly, vitamin D treatment can be effective at reducing ASD symptoms. Upon receiving daily doses of 300 IU vitamin D3 per kg bodyweight orally, 67 out of 83 children with ASD experienced improved symptoms [110]. The positive effect of vitamin D was most prominent in the group with 25(OH)D levels above 40 ng/mL at the end of the study, suggesting higher vitamin D levels correlate with increased improvement of behavior. Although research is limited, recent studies on the effect of vitamin D treatment in ASD children show promising results.
A review supported the need of a high vitamin D dose for its efficacy [31]. Whereas the recommended daily intake of vitamin D is 30 ng/mL, a minimum dose of 40–80 ng/mL is suggested for vitamin D to exert its immunomodulatory effects in general. In ASD, most improved ASD symptoms upon vitamin D administration above 40 ng/mL. Worldwide it is estimated that 30% of all children and adults are vitamin D deficient, and around 60% has insufficient vitamin D levels [110]. This high percentage of insufficiency cases illustrates the need for vitamin D supplementation and/or increased sun exposure when the effect of vitamin D on the immune system is wished upon. Presumably, this would not cause adverse effects as studies on the toxicity of vitamin D have found little disease outcomes, except possibly hypercalcemia [111]. However, findings on hypercalcemia are inconsistent and it is thus not known whether hypercalcemia will indeed occur in the case of vitamin D levels above 40–80 ng/mL and most likely at a dose of 150 ng/mL [3, 91].
All in all, many clinical trials have been performed on the association between vitamin D and ASD. Low vitamin D levels are observed more often in ASD children compared to healthy children. Moreover, research indicates the role of maternal vitamin D deficiency in ASD is plausible and recent studies have illustrated the effectiveness of vitamin D treatment on improving ASD symptoms. Thus, clinical trials show promising results on the association between vitamin D and ASD and the effectiveness of vitamin D treatment in ASD patients. Lastly, rather than in ASD children there is still little research performed on immune functioning and vitamin D levels in adults with ASD as lower 25(OH)D levels were observed in adults with autistic disorder compared to healthy individuals [112]. The lack of research in this target group complicates extrapolation of the discussed results to adults. It is therefore uncertain whether vitamin D supplementation could improve ASD symptoms in adults.
The association between vitamin D and ASD is proven through clinical research. Clinical trials show promising results on vitamin D supplementation and the improvement of ASD symptoms. Characteristics of ASD, including behavioral deficits and impaired communicative functioning, impair the lifestyle of both patients and their close relatives – improvement of symptoms therefore would be highly beneficial [113]. Insights into the mechanisms would support a better understanding of the etiology of the disorder. Consequently, this can enhance the finding of better preventive measures and treatments. Besides the lack of research into the mechanisms behind the effect of vitamin D on ASD, further research is also required to better understand immunomodulatory properties of vitamin D in general, as well as immune dysfunction in individuals with ASD [31]. Similarly, there is a lack of research on several important cytokines in ASD patients, like IL-21, IL-22 and IL-35. Additionally, IL-10 expression in ASD patients remains debatable. Different studies have found either reduced, similar or increased IL-10 levels compared to healthy individuals. This suggests the high interpersonal variability between ASD patients and the heterogeneous etiology of the disorder, emphasizing the need for further research to determine possible subgroups on which tailored treatment design could be based [114]. In addition, the role of IL-2 in regulating immune responses in ASD remains elusive. IL-2 is a Th1 cytokine, important for T cell proliferation of effector T cells but also for regulatory T cells. Vitamin D is shown to reduce IL-2 levels. This implies a reduction in Th1 cytokines, but as IL-2 is required for TGF-ß-mediated induction of CTLA-4 and Foxp3 expression on Tregs this suggests that increased IL-2 expression would enhance immunosuppression [115, 116, 117].
Although research on the association between vitamin D and ASD is receiving increased attention, no causality has been proven. As discussed, it is unknown whether vitamin D deficiency is caused by genetic or environmental factors. The possibility of reduced endogenous vitamin D production in ASD patients raises the question whether vitamin D insufficiency is a cause or consequence of ASD. To date, it is uncertain whether vitamin D deficiency predisposes ASD onset or is developed because of ASD. Effectiveness of vitamin D supplementation is irrespective of the outcome of causality, as clinical trials have shown promising results on the positive effect of vitamin D on ASD symptoms. However, increasing sun exposure could be less effective in the case of impaired endogenous vitamin D production in ASD patients. Research on the mechanisms behind the role of vitamin D in ASD could support a better understanding of a possible causal relationship.
Vitamin D can have immunosuppressive effects on the immune system that could be of interest in ASD. By shifting immune responses away from Th1- and Th17-mediated towards Th2- and Treg-mediated, vitamin D promotes a tolerogenic state in the immune system. This could rebalance immune dysregulation in ASD, consequently reducing systemic inflammation among others. Clinical trials on the effect of vitamin D supplementation on improving ASD symptoms and reducing ASD risk are promising, highlighting the relevance of investigating vitamin D when studying ASD. This relevance is best illustrated by the finding that increased immune activity is positively correlated with severity of ASD symptoms, a process which could be counteracted by vitamin D. However, studies on the direct mechanisms of vitamin D on the immune system in ASD patients are absent. Therefore, further research is necessary to draw conclusions about a possible causal relationship. Moreover, further research into the mechanisms behind maternal vitamin deficiency and neuroinflammation are advised to investigate possible preventive actions of vitamin D in relation to ASD. Since vitamin D toxicity is rare, it is advised to increase vitamin D levels in pregnant women and ASD patients. However, insufficient research exists to state the effectiveness of vitamin D in regulating immune dysregulation in ASD patients with confidence.
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On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. 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After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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The presented biological wastewater treatment processes include: (1) bioremediation of wastewater that includes aerobic treatment (oxidation ponds, aeration lagoons, aerobic bioreactors, activated sludge, percolating or trickling filters, biological filters, rotating biological contactors, biological removal of nutrients) and anaerobic treatment (anaerobic bioreactors, anaerobic lagoons); (2) phytoremediation of wastewater that includes constructed wetlands, rhizofiltration, rhizodegradation, phytodegradation, phytoaccumulation, phytotransformation, and hyperaccumulators; and (3) mycoremediation of wastewater. The discussed chemical wastewater treatment processes include chemical precipitation (coagulation, flocculation), ion exchange, neutralization, adsorption, and disinfection (chlorination/dechlorination, ozone, UV light). Additionally, this chapter elucidates and illustrates the wastewater treatment plants in terms of plant sizing, plant layout, plant design, and plant location.",book:{id:"4619",slug:"wastewater-treatment-engineering",title:"Wastewater Treatment Engineering",fullTitle:"Wastewater Treatment Engineering"},signatures:"Mohamed Samer",authors:[{id:"175050",title:"Prof.",name:"Mohamed",middleName:null,surname:"Samer",slug:"mohamed-samer",fullName:"Mohamed Samer"}]},{id:"48803",doi:"10.5772/60770",title:"Bioremediation of Polluted Waters Using Microorganisms",slug:"bioremediation-of-polluted-waters-using-microorganisms",totalDownloads:11381,totalCrossrefCites:36,totalDimensionsCites:79,abstract:"Water pollution is an issue of great concern worldwide, and it can be broadly divided into three main categories, that is, contamination by organic compounds, inorganic compounds (e.g., heavy metals), and microorganisms. In recent years, the number of research studies concerning the use of efficient processes to clean up and minimize the pollution of water bodies has been increasing. In this context, the use of bioremediation processes for the removal of toxic metals from aqueous solutions is gaining considerable attention. Bioremediation can be defined as the ability of certain biomolecules or types of biomass to bind and concentrate selected ions or other molecules present in aqueous solutions. Bioremediation using microorganisms shows great potential for future development due to its environmental compatibility and possible cost-effectiveness. A wide range of microorganisms, including bacteria, fungi, yeasts, and algae, can act as biologically active methylators, which are able to at least modify toxic species. Many microbial detoxification processes involve the efflux or exclusion of metal ions from the cell, which in some cases can result in high local concentrations of metals at the cell surface, where they can react with biogenic ligands and precipitate. Although microorganisms cannot destroy metals, they can alter their chemical properties via a surprising array of mechanisms. The main purpose of this chapter is to provide an update on the recent literature concerning the strategies available for the remediation of metal-contaminated water bodies using microorganisms and to critically discuss their main advantages and weaknesses. The focus is on the heavy metals associated with environmental contamination, for instance, lead (Pb), cadmium (Cd), and chromium (Cr), which are potentially hazardous to ecosystems. The types of microorganisms that are used in bioremediation processes due to their natural capacity to biosorb toxic heavy metal ions are discussed in detail. This chapter summarizes existing knowledge on various aspects of the fundamentals and applications of bioremediation and critically reviews the obstacles to its commercial success and future perspectives.",book:{id:"4602",slug:"advances-in-bioremediation-of-wastewater-and-polluted-soil",title:"Advances in Bioremediation of Wastewater and Polluted Soil",fullTitle:"Advances in Bioremediation of Wastewater and Polluted Soil"},signatures:"Luciene M. Coelho, Helen C. Rezende, Luciana M. Coelho, Priscila\nA.R. de Sousa, Danielle F.O. Melo and Nívia M.M. Coelho",authors:[{id:"163731",title:"Prof.",name:"Nivia",middleName:null,surname:"Coelho",slug:"nivia-coelho",fullName:"Nivia Coelho"},{id:"177651",title:"Dr.",name:"Luciana",middleName:null,surname:"Coelho",slug:"luciana-coelho",fullName:"Luciana Coelho"},{id:"177741",title:"Dr.",name:"Luciene M.",middleName:null,surname:"Coelho",slug:"luciene-m.-coelho",fullName:"Luciene M. Coelho"},{id:"177742",title:"Dr.",name:"Helen C.",middleName:null,surname:"Rezende",slug:"helen-c.-rezende",fullName:"Helen C. Rezende"},{id:"177743",title:"Dr.",name:"Priscila A.R.",middleName:null,surname:"de Sousa",slug:"priscila-a.r.-de-sousa",fullName:"Priscila A.R. de Sousa"},{id:"177744",title:"Dr.",name:"Danielle F.O.",middleName:null,surname:"Melo",slug:"danielle-f.o.-melo",fullName:"Danielle F.O. Melo"}]},{id:"41953",doi:"10.5772/52665",title:"Treatment Technologies for Organic Wastewater",slug:"treatment-technologies-for-organic-wastewater",totalDownloads:10682,totalCrossrefCites:25,totalDimensionsCites:75,abstract:null,book:{id:"2503",slug:"water-treatment",title:"Water Treatment",fullTitle:"Water Treatment"},signatures:"Chunli Zheng, Ling Zhao, Xiaobai Zhou, Zhimin Fu and An Li",authors:[{id:"141286",title:"Dr",name:"An",middleName:null,surname:"Li",slug:"an-li",fullName:"An Li"},{id:"155298",title:"Dr.",name:"Chunli",middleName:null,surname:"Zheng",slug:"chunli-zheng",fullName:"Chunli Zheng"},{id:"155299",title:"Dr.",name:"Ling",middleName:null,surname:"Zhao",slug:"ling-zhao",fullName:"Ling Zhao"},{id:"155300",title:"Dr.",name:"Xiaobai",middleName:null,surname:"Zhou",slug:"xiaobai-zhou",fullName:"Xiaobai Zhou"},{id:"155301",title:"Dr.",name:"Zhimin",middleName:null,surname:"Fu",slug:"zhimin-fu",fullName:"Zhimin Fu"}]},{id:"30860",doi:"10.5772/36310",title:"Use of Agro-Industrial Wastes in Solid-State Fermentation Processes",slug:"use-of-agro-industrial-wastes-in-solid-state-fermentation-processes",totalDownloads:4176,totalCrossrefCites:9,totalDimensionsCites:66,abstract:null,book:{id:"1868",slug:"industrial-waste",title:"Industrial Waste",fullTitle:"Industrial Waste"},signatures:"Solange I. Mussatto, Lina F. Ballesteros, Silvia Martins and José A. Teixeira",authors:[{id:"107810",title:"Dr.",name:"Solange I.",middleName:null,surname:"Mussatto",slug:"solange-i.-mussatto",fullName:"Solange I. Mussatto"},{id:"109520",title:"MSc.",name:"Lina F.",middleName:null,surname:"Ballesteros",slug:"lina-f.-ballesteros",fullName:"Lina F. Ballesteros"},{id:"109522",title:"MSc.",name:"Silvia",middleName:null,surname:"Martins",slug:"silvia-martins",fullName:"Silvia Martins"},{id:"109523",title:"Prof.",name:"José António",middleName:null,surname:"Teixeira",slug:"jose-antonio-teixeira",fullName:"José António Teixeira"}]}],mostDownloadedChaptersLast30Days:[{id:"49024",title:"Biological and Chemical Wastewater Treatment Processes",slug:"biological-and-chemical-wastewater-treatment-processes",totalDownloads:27708,totalCrossrefCites:55,totalDimensionsCites:103,abstract:"This chapter elucidates the technologies of biological and chemical wastewater treatment processes. The presented biological wastewater treatment processes include: (1) bioremediation of wastewater that includes aerobic treatment (oxidation ponds, aeration lagoons, aerobic bioreactors, activated sludge, percolating or trickling filters, biological filters, rotating biological contactors, biological removal of nutrients) and anaerobic treatment (anaerobic bioreactors, anaerobic lagoons); (2) phytoremediation of wastewater that includes constructed wetlands, rhizofiltration, rhizodegradation, phytodegradation, phytoaccumulation, phytotransformation, and hyperaccumulators; and (3) mycoremediation of wastewater. The discussed chemical wastewater treatment processes include chemical precipitation (coagulation, flocculation), ion exchange, neutralization, adsorption, and disinfection (chlorination/dechlorination, ozone, UV light). Additionally, this chapter elucidates and illustrates the wastewater treatment plants in terms of plant sizing, plant layout, plant design, and plant location.",book:{id:"4619",slug:"wastewater-treatment-engineering",title:"Wastewater Treatment Engineering",fullTitle:"Wastewater Treatment Engineering"},signatures:"Mohamed Samer",authors:[{id:"175050",title:"Prof.",name:"Mohamed",middleName:null,surname:"Samer",slug:"mohamed-samer",fullName:"Mohamed Samer"}]},{id:"52474",title:"Slaughterhouse Wastewater: Treatment, Management and Resource Recovery",slug:"slaughterhouse-wastewater-treatment-management-and-resource-recovery",totalDownloads:6763,totalCrossrefCites:18,totalDimensionsCites:49,abstract:"The meat processing industry is one of the largest consumers of total freshwater used in the agricultural and livestock industry worldwide. Meat processing plants (MPPs) produce large amounts of slaughterhouse wastewater (SWW) because of the slaughtering process and cleaning of facilities. SWWs need significant treatment for a sustainable and safe discharge to the environment due to the high content of organics and nutrients. Therefore, the treatment and final disposal of SWW are a public health necessity. In this chapter, the regulatory frameworks relevant to the SWW management, environmental impacts, health effects, and treatment methods are discussed. Although physical, chemical, and biological treatment can be used for SWW degradation, each treatment process has different advantages and drawbacks depending on the SWW characteristics, best available technology, jurisdictions, and regulations. SWWs are typically assessed using bulk parameters because of the various pollutant loads derived from the type and the number of animals slaughtered that fluctuate amid the meat industry. Thus, an on-site treatment using combined processes would be the best option to treat and disinfect the slaughterhouse effluents to be safely discharged into receiving waters.",book:{id:"6050",slug:"physico-chemical-wastewater-treatment-and-resource-recovery",title:"Physico-Chemical Wastewater Treatment and Resource Recovery",fullTitle:"Physico-Chemical Wastewater Treatment and Resource Recovery"},signatures:"Ciro Bustillo-Lecompte and Mehrab Mehrvar",authors:[{id:"66753",title:"Prof.",name:"Mehrab",middleName:null,surname:"Mehrvar",slug:"mehrab-mehrvar",fullName:"Mehrab Mehrvar"},{id:"189304",title:"Dr.",name:"Ciro",middleName:"Fernando",surname:"Bustillo-Lecompte",slug:"ciro-bustillo-lecompte",fullName:"Ciro Bustillo-Lecompte"}]},{id:"48946",title:"Cogeneration Power-Desalting Plants Using Gas Turbine Combined Cycle",slug:"cogeneration-power-desalting-plants-using-gas-turbine-combined-cycle",totalDownloads:4586,totalCrossrefCites:8,totalDimensionsCites:10,abstract:"The gas-steam turbine combined cycle (GTCC) is the preferred power plant type because of its high efficiency and its use of cheap and clean natural gas as fuel. It is also the preferred type in the Arab Gulf countries where it is used as cogeneration power-desalting plant (CPDP). In this chapter, descriptions and analysis of the GTCC components are presented, namely, the gas turbine cycle (compressor, combustor, gas turbine), heat recovery steam generator, and steam turbine. Combinations of the GTCC with thermally driven desalination units to present CPDP are presented. A parametric study to show the effect of using GTCC on several operating parameters on the CPDP is also presented, as well as cost allocation methods of fuel between the two product utilities (electric power and desalted seawater are also presented).",book:{id:"4613",slug:"desalination-updates",title:"Desalination Updates",fullTitle:"Desalination Updates"},signatures:"M.A. Darwish, H.K. Abdulrahim, A.A. Mabrouk and A.S. Hassan",authors:[{id:"173364",title:"Prof.",name:"Mohamed",middleName:null,surname:"Darwish",slug:"mohamed-darwish",fullName:"Mohamed Darwish"},{id:"173603",title:"Dr.",name:"Hassan",middleName:null,surname:"Abdulrahim",slug:"hassan-abdulrahim",fullName:"Hassan Abdulrahim"},{id:"173774",title:"Dr.",name:"Abdel Nasser",middleName:null,surname:"Mabrouk",slug:"abdel-nasser-mabrouk",fullName:"Abdel Nasser Mabrouk"},{id:"175519",title:"Dr.",name:"Ashraf",middleName:null,surname:"Hassan",slug:"ashraf-hassan",fullName:"Ashraf Hassan"}]},{id:"54201",title:"Pulp Mill Wastewater: Characteristics and Treatment",slug:"pulp-mill-wastewater-characteristics-and-treatment",totalDownloads:4873,totalCrossrefCites:7,totalDimensionsCites:21,abstract:"The production of chemical pulp in recent times is 180 million tons per year; while the production of eucalyptus pulp has increased intensively, especially in the southern hemisphere. The pulp and paper industry has long been considered a large consumer of natural resources (wood and water) and one of the largest sources of pollution to the environment (air, water courses and soil). Important efforts are being made to reduce the pollutant levels and water consumption of the industry. The wastewater composition, and therefore, the efficiency of effluent treatments and characteristics of the discharges to water are strongly dependent on the applied technology and raw materials. Despite a large body of literature on softwood-based wastewater, few studies have examined the characteristics of kraft eucalyptus bleaching effluents and their behaviour in the different biological treatments. The largest secondary treatment systems today use the activated sludge process. Sixty to seventy-five per cent of all the biological effluent treatment plants within the pulp and paper industry use this kind of treatment system. This chapter reviews the current pulping technologies at mills and compares the chemical composition and biological treatment of wastewater between softwood and hardwood bleached pulps.",book:{id:"5417",slug:"biological-wastewater-treatment-and-resource-recovery",title:"Biological Wastewater Treatment and Resource Recovery",fullTitle:"Biological Wastewater Treatment and Resource Recovery"},signatures:"María Noel Cabrera",authors:[{id:"187931",title:"Dr.",name:"María Noel",middleName:null,surname:"Cabrera",slug:"maria-noel-cabrera",fullName:"María Noel Cabrera"}]},{id:"54320",title:"Phosphorus Recovery by Struvite Crystallization from Livestock Wastewater and Reuse as Fertilizer: A Review",slug:"phosphorus-recovery-by-struvite-crystallization-from-livestock-wastewater-and-reuse-as-fertilizer-a-",totalDownloads:2539,totalCrossrefCites:7,totalDimensionsCites:15,abstract:"In China, the intensive livestock farming produces massive livestock wastewater with high concentration of phosphorus. Discharge of these compounds to surface water not only causes water eutrophication but also wastes phosphorus resources for plant growth. Therefore, it’s necessary combining the removal of phosphorus from livestock wastewater with its recovery and reuse as fertilizer. As a valuable slow-release mineral fertilizer, struvite crystallization has become a focus in phosphorus recovery. In this chapter, struvite crystallization mechanism, reaction factors, crystallizers, and the applications of struvite as fertilizer are discussed. Two steps of nucleation and crystal growth for struvite crystallization from generation to growth are introduced. The reaction factors, including molar ratio of magnesium and phosphate, solution pH, coexisting substances, and seeding assist, of struvite crystallization are summarized. Several innovate types of crystallizer, which relate to the shape and size of harvest struvite to realize the phosphorus recycling, are demonstrated. Due to the influence of toxic or harmful impurities in struvite on its reuse as fertilizer, the environmental risk evaluation of struvite application is introduced. In conclusion, struvite crystallization is a promising tool for recovering phosphorus from livestock wastewater.",book:{id:"6050",slug:"physico-chemical-wastewater-treatment-and-resource-recovery",title:"Physico-Chemical Wastewater Treatment and Resource Recovery",fullTitle:"Physico-Chemical Wastewater Treatment and Resource Recovery"},signatures:"Tao Zhang, Rongfeng Jiang and Yaxin Deng",authors:[{id:"185487",title:"Associate Prof.",name:"Tao",middleName:null,surname:"Zhang",slug:"tao-zhang",fullName:"Tao Zhang"},{id:"195403",title:"Dr.",name:"Rongfeng",middleName:null,surname:"Jiang",slug:"rongfeng-jiang",fullName:"Rongfeng Jiang"},{id:"195404",title:"Dr.",name:"Yaxin",middleName:null,surname:"Deng",slug:"yaxin-deng",fullName:"Yaxin Deng"}]}],onlineFirstChaptersFilter:{topicId:"779",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:106,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517",scope:"Paralleling similar advances in the medical field, astounding advances occurred in Veterinary Medicine and Science in recent decades. These advances have helped foster better support for animal health, more humane animal production, and a better understanding of the physiology of endangered species to improve the assisted reproductive technologies or the pathogenesis of certain diseases, where animals can be used as models for human diseases (like cancer, degenerative diseases or fertility), and even as a guarantee of public health. Bridging Human, Animal, and Environmental health, the holistic and integrative “One Health” concept intimately associates the developments within those fields, projecting its advancements into practice. This book series aims to tackle various animal-related medicine and sciences fields, providing thematic volumes consisting of high-quality significant research directed to researchers and postgraduates. It aims to give us a glimpse into the new accomplishments in the Veterinary Medicine and Science field. By addressing hot topics in veterinary sciences, we aim to gather authoritative texts within each issue of this series, providing in-depth overviews and analysis for graduates, academics, and practitioners and foreseeing a deeper understanding of the subject. Forthcoming texts, written and edited by experienced researchers from both industry and academia, will also discuss scientific challenges faced today in Veterinary Medicine and Science. In brief, we hope that books in this series will provide accessible references for those interested or working in this field and encourage learning in a range of different topics.",coverUrl:"https://cdn.intechopen.com/series/covers/13.jpg",latestPublicationDate:"June 29th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:11,editor:{id:"38652",title:"Prof.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",institutionURL:null,country:{name:"Portugal"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"19",title:"Animal Science",coverUrl:"https://cdn.intechopen.com/series_topics/covers/19.jpg",isOpenForSubmission:!0,editor:{id:"259298",title:"Dr.",name:"Edward",middleName:null,surname:"Narayan",slug:"edward-narayan",fullName:"Edward Narayan",profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",biography:"Dr. Edward Narayan graduated with Ph.D. degree in Biology from the University of the South Pacific and pioneered non-invasive reproductive and stress endocrinology tools for amphibians - the novel development and validation of non-invasive enzyme immunoassays for the evaluation of reproductive hormonal cycle and stress hormone responses to environmental stressors. \nDr. Narayan leads the Stress Lab (Comparative Physiology and Endocrinology) at the University of Queensland. A dynamic career research platform which is based on the thematic areas of comparative vertebrate physiology, stress endocrinology, reproductive endocrinology, animal health and welfare, and conservation biology. \nEdward has supervised 40 research students and published over 60 peer reviewed research.",institutionString:null,institution:{name:"University of Queensland",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null},{id:"20",title:"Animal Nutrition",coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",isOpenForSubmission:!0,editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",slug:"manuel-gonzalez-ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",biography:"Dr. Manuel González Ronquillo obtained his doctorate degree from the University of Zaragoza, Spain, in 2001. He is a research professor at the Faculty of Veterinary Medicine and Animal Husbandry, Autonomous University of the State of Mexico. He is also a level-2 researcher. He received a Fulbright-Garcia Robles fellowship for a postdoctoral stay at the US Dairy Forage Research Center, Madison, Wisconsin, USA in 2008–2009. He received grants from Alianza del Pacifico for a stay at the University of Magallanes, Chile, in 2014, and from Consejo Nacional de Ciencia y Tecnología (CONACyT) to work in the Food and Agriculture Organization’s Animal Production and Health Division (AGA), Rome, Italy, in 2014–2015. He has collaborated with researchers from different countries and published ninety-eight journal articles. 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He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. 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